ArticleBlood2012
Contrasting acute graft-versus-host disease effects of Tim-3/galectin-9 pathway blockade dependent upon the presence of donor regulatory T cells.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- The Role of Biomarkers in the Diagnosis and Risk Stratification of Acute Graft-versus-Host Disease: A Systematic Review.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2016Pooled it
- Trial
- Decreased galectin-9 and increased Tim-3 expression are related to poor prognosis in gastric cancer.PloS one · 2013Trial
- Novel approaches for separating graft-versus-leukemia effects from graft-versus-host disease.Frontiers in oncology · 2026Review
- TIM-3 blockade enhances ex vivo stimulated allogeneic NK cell therapy for relapsed murine neuroblastoma after hematopoietic cell transplant.Journal for immunotherapy of cancer · 2025Article
- Article
- Utilization of Clinical Data and Evaluation of Biomarkers in the Investigation of Graft-Versus-Host Disease Outcomes.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Biochemical markers and emerging therapies for intestinal manifestation of graft-versus-host disease.Frontiers in immunology · 2025Review
- Oncogene-induced TIM-3 ligand expression dictates susceptibility to anti-TIM-3 therapy in mice.The Journal of clinical investigation · 2024Article
- Hematopoietic Stem Cells and Their Niche in Bone Marrow.International journal of molecular sciences · 2024Review
- Chemotherapy-induced intestinal epithelial damage directly promotes galectin-9-driven modulation of T cell behavior.iScience · 2024Article
- Galectin-3 expression in donor T cells reduces GvHD severity and lethality after allogeneic hematopoietic cell transplantation.Cell reports · 2023Article
- Resolution of Inflammation in Acute Graft-Versus-Host-Disease: Advances and Perspectives.Biomolecules · 2022Review
- Intravenous Immunoglobulin Therapy Restores the Quantity and Phenotype of Circulating Dendritic Cells and CD4Frontiers in immunology · 2022Article
- Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors.Frontiers in immunology · 2020Review
- Dendritic Cell Expression of Retinal Aldehyde Dehydrogenase-2 Controls Graft-versus-Host Disease Lethality.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Biomarkers in Graft-Versus-Host Disease: from Prediction and Diagnosis to Insights into Complex Graft/Host Interactions.Current hematologic malignancy reports · 2018Review
- The Role of Co-stimulatory/Co-inhibitory Signals in Graft-vs.-Host Disease.Frontiers in immunology · 2018Review
- T Cell-Derived CD70 Delivers an Immune Checkpoint Function in Inflammatory T Cell Responses.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Allogeneic stem cell transplantation in fully MHC-matched Mauritian cynomolgus macaques recapitulates diverse human clinical outcomes.Nature communications · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
T-cell immunoglobulin mucin-3 (Tim-3) is expressed on pathogenic T cells, and its ligand galectin-9 (gal-9) is up-regulated in inflamed tissues. When Tim-3(+) T cells encounter high gal-9 levels, they are deleted. Tim-3 is up-regulated on activated T cells during GVHD. Inhibition of Tim-3/gal-9 binding by infusion of a Tim-3-Ig fusion protein or Tim-3(-/-) donor T cells increased T-cell proliferation and GVHD lethality. When the Tim-3/gal-9 pathway engagement was augmented using gal-9 transgenic recipients, GVHD lethality was slowed. Together, these data indicate a potential for modulating this pathway to reduce disease by increasing Tim-3 or gal-9 engagement. Paradoxically, when Tim-3/gal-9 was inhibited in the absence of donor T-regulatory cells (Tregs), GVHD was inhibited. GVHD reduction was associated with decreased colonic inflammatory cytokines as well as epithelial barrier destruction. CD25-depleted Tim-3(-/-) donor T cells underwent increased activation-induced cell death because of increased IFN-γ production. To our knowledge, these studies are the first to show that although the absence of Tim-3/gal-9 pathway interactions augments systemic GVHD, concurrent donor Treg depletion paradoxically and surprisingly inhibits GVHD. Thus, although donor Tregs typically inhibit GVHD, under some conditions, such Tregs actually may contribute to GVHD by reducing activation-induced T-cell death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.